Search PubMed⌕ Search

Biomedical subjects

M Ward

Publications and source records attributed to M Ward.

At least 19 recordsLinked to original sources

Current chronic kidney disease practice patterns in the UK: a national survey.

BACKGROUND: There is an increasing focus on improving the detection and management of patients with chronic kidney disease (CKD). Data on CKD prevalence based on population sampling are now available, but there are few data about CKD patients attending nephrology services or how such services are organized. AIM: To survey services for CKD patients nationally. METHODS: A pre-piloted questionnaire was sent to all 72 renal units in the UK, referring to the situation in June 2004. RESULTS: Seventy units (97%) responded. The median ratio of prevalent CKD patients/prevalent renal replacement therapy (RRT) patients in the 25 units with data was 3.7 (IQR 2.7-5.7) and the median ratio of CKD stage 4 and 5 patients/prevalent RRT patients was 0.6 (IQR 0.4-1.1). This gives an estimated 140 000 CKD patients under the care of UK nephrologists, with 23 000 at CKD stage 4 or 5 (excluding those on RRT). Very few units had a full complement of the recommended multi-skilled renal team. Counsellors and psychologist were the most common perceived shortages. Of 70 responding units, 50 (74%) were using low clearance clinics for management of advanced CKD patients. Elective dialysis access services often had long delays, with median waiting time for vascular access ranging between 1 and 36 weeks, and for Tenchkoff catheter, between 0 and 12 weeks. DISCUSSION: CKD patients are a significant workload for UK nephrologists. Current provision of service is variable, and services need to be re-designed to cope with the expected future increase of referral of CKD patients.

Chronic Disease↗

Prostate specific antigen isoforms and human glandular kallikrein 2--which offers the best screening performance in a predominantly black population?

PURPOSE: Free prostate specific antigen, complexed PSA and human glandular kallikrein 2 have independently been tested against the gold standard of total PSA for prostate cancer screening in largely white populations. With the incidence of prostate cancer much higher in black men, we sought to evaluate these markers simultaneously in a predominantly black population. MATERIALS AND METHODS: A total of 138 men, of whom 108 were black, underwent ultrasound guided biopsy of the prostate for tPSA levels greater than 2.5 ng/ml or an abnormal digital rectal examination. Sera were drawn before biopsy and analyzed for tPSA, fPSA, cPSA and hK2 concentrations using standard methods (hK2 assay is for research use only, not for use in diagnostic procedures). The areas under the receiver operator characteristic curves were determined for each marker as well as biomarker combinations. Additionally, each parameter's specificity, positive and negative predictive values, and theoretical screening efficiency were assessed at or above the 95% sensitivity level. RESULTS: A total of 43 (31.1%) men had prostate cancer by biopsy. While the AUC for %fPSA was statistically the highest (0.822, p <0.001), cPSA offered the highest specificity (31.6%) and positive predictive power (31.7%) of any of the tested biomarkers at comparable sensitivity (greater than 95%). The calculated efficiency of cPSA (51.4%) was also higher than the other markers. Nearly 20% of biopsies would be avoided using cPSA vs standard tPSA screening methods. CONCLUSIONS: Comparing the major PSA isoforms and hK2, cPSA alone appears to offer superior diagnostic discrimination for cancer detection in a predominantly black population.

Black or African American↗

Proteome-based plasma biomarkers for Alzheimer's disease.

Alzheimer's disease is a common and devastating disease for which there is no readily available biomarker to aid diagnosis or to monitor disease progression. Biomarkers have been sought in CSF but no previous study has used two-dimensional gel electrophoresis coupled with mass spectrometry to seek biomarkers in peripheral tissue. We performed a case-control study of plasma using this proteomics approach to identify proteins that differ in the disease state relative to aged controls. For discovery-phase proteomics analysis, 50 people with Alzheimer's dementia were recruited through secondary services and 50 normal elderly controls through primary care. For validation purposes a total of 511 subjects with Alzheimer's disease and other neurodegenerative diseases and normal elderly controls were examined. Image analysis of the protein distribution of the gels alone identifies disease cases with 56% sensitivity and 80% specificity. Mass spectrometric analysis of the changes observed in two-dimensional electrophoresis identified a number of proteins previously implicated in the disease pathology, including complement factor H (CFH) precursor and alpha-2-macroglobulin (alpha-2M). Using semi-quantitative immunoblotting, the elevation of CFH and alpha-2M was shown to be specific for Alzheimer's disease and to correlate with disease severity although alternative assays would be necessary to improve sensitivity and specificity. These findings suggest that blood may be a rich source for biomarkers of Alzheimer's disease and that CFH, together with other proteins such as alpha-2M may be a specific markers of this illness.

Aged↗

Hepatitis A vaccination policy for travellers to Egypt in eight European countries, 2004.

In 2004, an outbreak of hepatitis A occurred in European tourists returning from Egypt. The reported hepatitis A attack rates varied considerably between tourists from different European countries. To determine the reason for this divergence in attack rates, a survey was undertaken with the following objectives: (a) documentation of national hepatitis A prevention policies for people travelling to Egypt and (b) documentation of hepatitis A reporting practices in these countries. A questionnaire was compiled and distributed to 13 European countries. All eight of the countries that responded had produced guidelines for the prevention of travel-associated hepatitis A. Between 2001-2003, 40% (range 4-51) of hepatitis A cases reported annually were associated with travel abroad. This occurred despite the fact that all countries recommended active vaccination with hepatitis A vaccine for people travelling to Egypt for holidays. There was no standard case definition for reporting confirmed cases in the countries that reported hepatitis A cases. As it is likely that travel-associated infections will increase as more people take overseas holidays, innovative ways to increase the number of travellers who seek and adhere to appropriate medical advice prior to travel must be explored. In addition, we recommend the use of the European Commission case definition for notification of confirmed cases of hepatitis A.

Egypt↗

Epidemiological findings and medical, legal, and public health challenges of an investigation of severe soft tissue infections and deaths among injecting drug users -- Ireland, 2000.

In May 2000, public health authorities in Dublin, Ireland, identified a cluster of unexplained severe illness among injecting drug users (IDUs). Similar clusters were also reported in Scotland and England. Concurrent investigations were undertaken to identify the aetiology and source of the illnesses. In Dublin, 22 IDUs were identified with injection-site inflammation resulting in hospitalization or death; eight (36%) died. Common clinical findings among patients with severe systemic symptoms included leukaemoid reaction and cardiogenic shock. Seventeen (77%) patients reported injecting heroin intramuscularly in the 2 weeks before illness. Of 11 patients with adequate specimens available for testing, two (18%) were positive by 16S rDNA PCR for Clostridium novyi. Clinical and laboratory findings suggested that histotoxic Clostridia caused a subset of infections in these related clusters. Empiric treatment for infections among IDUs was optimized for anaerobic organisms, and outreach led to increased enrolment in methadone treatment in Dublin. Many unique legal, medical, and public health challenges were encountered during the investigation of this outbreak.

Adult↗

A simple cardiovascular risk score can predict poor outcome in non-heart-beating donor renal transplantation.

A simple cardiovascular risk score used in our centre to plan cardiovascular work-up for renal transplantation can predict outcome in non-heart-beating donor (NHBD) renal transplantation. Patients in the higher-risk group, with a score of >12 of a maximum of 36 are likely to have a longer duration of delayed graft function, poorer glomerular filtration rate at 6 months, and inferior graft and patient survival, together with a relative rate of graft loss within 60 days of 4.514 (P = .019) and within 1 year of 3.511 (P = .036). Although a high cardiovascular risk score should not be regarded as a contraindication to NHBD transplantation, the score can be used to facilitate recipient selection.

Adult↗

Cardiovascular risk assessment scoring system for the determination of cardiovascular mortality in renal transplant patients.

It is well known that the greatest risk for mortality post-renal transplant is cardiovascular death. We compared a modified cardiac risk assessment system among renal transplant patients who subsequently died versus the group that survived. There was a good correlation between the low, medium, and high scores with survival. The deceased group had significantly greater cardiovascular scores than case controls.

Adult↗

A simple cardiovascular risk score can predict poor outcome in NHBD renal transplantation.

A simple cardiovascular risk score used in our center to plan cardiovascular workup for renal transplantation can predict outcome in non-heart-beating donor (NHBD) renal transplantation. Patients in the higher risk group, with a score of >12 out of a maximum of 36 are likely to have a longer duration of delayed graft function, poorer glomerular filtration rate at 6 months, and inferior graft and patient survival, together with an relative rate of graft loss within 60 days of >4 (P = .053). Although a high cardiovascular risk score should not be regarded as a contraindication to NHBD transplantation, the score can be used to facilitate recipient selection.

Adult↗

To self, or not to self... a review of outcrossing and pollen-mediated gene flow in neotropical trees.

Despite the typically low population densities and animal-mediated pollination of tropical forest trees, outcrossing and long-distance pollen dispersal are the norm. We reviewed the genetic literature on mating systems and pollen dispersal for neotropical trees to identify the ecological and phylogenetic correlates. The 36 studies surveyed found >90% outcrossed mating for 45 hermaphroditic or monoecious species. Self-fertilization rates varied inversely with population density and showed phylogenetic and geographic trends. The few direct measures of pollen flow (N=11 studies) suggest that pollen dispersal is widespread among low-density tropical trees, ranging from a mean of 200 m to over 19 km for species pollinated by small insects or bats. Future research needs to examine (1) the effect of inbreeding depression on observed outcrossing rates, (2) pollen dispersal in a wide range of pollination syndromes and ecological classes, (3) and the range of variation of mating system expression at different hierarchical levels, including individual, seasonal, population, ecological, landscape and range wide.

Genetic Markers↗

Genetic resource impacts of habitat loss and degradation; reconciling empirical evidence and predicted theory for neotropical trees.

The theoretical impacts of anthropogenic habitat degradation on genetic resources have been well articulated. Here we use a simulation approach to assess the magnitude of expected genetic change, and review 31 studies of 23 neotropical tree species to assess whether empirical case studies conform to theory. Major differences in the sensitivity of measures to detect the genetic health of degraded populations were obvious. Most studies employing genetic diversity (nine out of 13) found no significant consequences, yet most that assessed progeny inbreeding (six out of eight), reproductive output (seven out of 10) and fitness (all six) highlighted significant impacts. These observations are in line with theory, where inbreeding is observed immediately following impact, but genetic diversity is lost slowly over subsequent generations, which for trees may take decades. Studies also highlight the ecological, not just genetic, consequences of habitat degradation that can cause reduced seed set and progeny fitness. Unexpectedly, two studies examining pollen flow using paternity analysis highlight an extensive network of gene flow at smaller spatial scales (less than 10 km). Gene flow can thus mitigate against loss of genetic diversity and assist in long-term population viability, even in degraded landscapes. Unfortunately, the surveyed studies were too few and heterogeneous to examine concepts of population size thresholds and genetic resilience in relation to life history. Future suggested research priorities include undertaking integrated studies on a range of species in the same landscapes; better documentation of the extent and duration of impact; and most importantly, combining neutral marker, pollination dynamics, ecological consequences, and progeny fitness assessment within single studies.

Computer Simulation↗

Central dose data management and analysis in IT-driven radiation protection strategies.

The applications of information technology in health care are now widespread and continue to grow. Medical imaging is at the forefront of this revolution and the introduction of digital detection methods to replace film is now addressing the diagnostic X-ray market, the most routinely employed imaging modality. The introduction of picture archiving and communication systems, hospital and radiology information systems is well underway, and the integration of radiation protection initiatives into these developments is desirable. In north-west UK, a project aimed at developing and implementing IT-driven radiation protection strategies has been underway for the past 10 y. Such strategies are geared towards the support of European Commission patient dose directive 97/43 EURATOM, in particular the need to implement clinical audit, patient dose audit and to establish dose reference levels. This paper demonstrates the national and local requirements for establishing a central dose data management system for use in radiation protection strategies. In particular, such a system can help develop and support the role of a medical physics expert in optimisation. The scientific requirements for such an approach are presented in this paper, and a prototype system is described. Preliminary results obtained with the central data management facility are also presented and the implication for analysing multiple site dose data in optimisation strategies for digital radiographic technology is highlighted.

Calibration↗

The effectiveness of stand alone air cleaners for shelter-in-place.

UNLABELLED: Stand-alone air cleaners may be efficient for rapid removal of indoor fine particles and have potential use for shelter-in-place (SIP) strategies following acts of bioterrorism. A screening model was employed to ascertain the potential significance of size-resolved particle (0.1-2 microm) removal using portable high efficiency particle arresting (HEPA) air cleaners in residential buildings following an outdoor release of particles. The number of stand-alone air cleaners, air exchange rate, volumetric flow rate through the heating, ventilating and air-conditioning (HVAC) system, and size-resolved particle removal efficiency in the HVAC filter were varied. The effectiveness of air cleaners for SIP was evaluated in terms of the outdoor and the indoor particle concentration with air cleaner(s) relative to the indoor concentration without air cleaners. Through transient and steady-state analysis of the model it was determined that one to three portable HEPA air cleaners can be effective for SIP following outdoor bioaerosol releases, with maximum reductions in particle concentrations as high as 90% relative to conditions in which an air cleaner is not employed. The relative effectiveness of HEPA air cleaners vs. other removal mechanisms was predicted to decrease with increasing particle size, because of increasing competition by particle deposition with indoor surfaces and removal to HVAC filters. However, the effect of particle size was relatively small for most scenarios considered here. PRACTICAL IMPLICATIONS: The results of a screening analysis suggest that stand-alone (portable) air cleaners that contain high efficiency particle arresting (HEPA) filters can be effective for reducing indoor fine particle concentrations in residential dwellings during outdoor releases of biological warfare agents. The relative effectiveness of stand-alone air cleaners for reducing occupants' exposure to particles of outdoor origin depends on several factors, including the type of heating, ventilating and air-conditioning (HVAC) filter, HVAC operation, building air exchange rate, particle size, and duration of elevated outdoor particle concentration. Maximum particle reductions, relative to no stand-alone air cleaners, of 90% are predicted when three stand-alone air cleaners are employed.

Aerosols↗

Electronic reporting improves timeliness and completeness of infectious disease notification, The Netherlands, 2003.

In 2002, the internet based reporting system OSIRIS was introduced in the Netherlands and by the end of that year had fully replaced the paper-based reporting system. The objectives of OSIRIS were to improve timeliness and completeness of surveillance data on infectious diseases reported from regional to national level. We compared the timeliness of infectious diseases reported by the conventional paper-based system in 2001 with those reported by OSIRIS in 2003. Two distinct types of delay were compared: (1) total delay: defined as time between symptom onset and reporting at national level and (2) central delay: defined as time between regional and national reporting. Median delays between both systems were compared using the Wilcoxon Rank Sum-Test. We also compared electronic reports received via OSIRIS in 2003 to those received through the conventional system for 2001 for completeness of specific data fields. The Fisher exact test and the Mantel-Haenzel test with Yates correction were used to determine the significance of proportions of completed data fields in each system. Results showed the median central delay was significantly reduced for all diseases in OSIRIS compared to conventional reporting system. Overall, the median central delay was reduced from 10 days (interquartile range 4) in 2001 to 1 day (interquartile range 1) in 2003. Except for cases of malaria, the total delay, from symptom onset to national reporting, was also significantly reduced. In addition, OSIRIS records contained more complete information than conventional records. In total, in 2003, 92.3% of data field examined were complete compared with 81.3% in 2001. This study documents the benefits of electronic reporting of infectious disease surveillance data in terms of improved timeliness and completeness.

Clinical Laboratory Information Systems↗

The coronary baroreflex in humans.

Previous studies have identified the presence of coronary baroreceptors in animal models. We set up a study to explore the presence of coronary baroreceptors in humans, which was performed with isolated, graded aortic root perfusion in patients during cardiopulmonary bypass. With ethical approval 12 patients with normal coronary arteries, aged 58-75 (mean 69) years undergoing mitral valve surgery were recruited to the study with informed consent. Those with aortic valve incompetence, coronary, or peripheral artery disease and diabetes mellitus were excluded. They were randomized to have their coronary perfusion pressure set low at 50 mmHg for 90 seconds and then adjusted high to 80 mmHg for 90 seconds (group L-H) or the reverse sequence (group H-L). Average arterial pressure and approximately constant systemic flow over 30-second periods were used to calculate vascular resistance (SVR). The first six experiments followed initiation of cardiopulmonary bypass and aortic clamping but before the delivery of cold blood cardioplegia; the blood temperature for these experiments was kept at 32 degrees C. The remaining six were conducted prior to removal of the aortic cross clamp at 37 degrees C. Coronary sinus blood samples were analyzed to exclude myocardial ischemia. Coronary sinus blood samples showed insignificant variation in oxygen saturation, lactate, and troponin T. Three patients were excluded because of unstable blood pressure. In the (L-H) group SVR reduced in 4 of 4 remaining patients (mean -9.4%, range -3.9 to -19.6%). In the (H-L) group SVR increased in three patients (mean +2.0%, range 1.1 to 3.7%) but decreased in two (-8.9% and -15.8%). These preliminary results, although not statistically different, suggest the presence of coronary baroreceptors in humans. The reflex vascular responses are similar to those previously reported in animal models.

Aged↗

Lack of association of matrix metalloproteinase 3 (MMP3) genotypes with ankylosing spondylitis susceptibility and severity.

OBJECTIVE: To study the linkage and association of ankylosing spondylitis (AS) with genotypes for matrix metalloproteinase 3 (MMP3), a gene located at chromosome 11q22.3 and lying within the 101-124 cM region observed in a recent genome-wide scan as a region associated with AS susceptibility. METHODS: MMP3 genotypes were examined in 229 pedigrees with AS, 131 sporadic AS cases and 87 Caucasian controls. Eight single-nucleotide polymorphisms (SNPs) were selected and genotyped using Taqman. Non-parametric linkage (NPL) analysis was conducted between the eight MMP3 SNPs and AS using the NPL-all statistic and two-point parametric linkage analysis using GeneHunter Plus. Unrelated AS cases and controls were compared using chi2 statistics, and family-based controls using the transmission disequilibrium test and pedigree disequilibrium test. RESULTS: None of the eight MMP3 SNPs were significantly associated with AS, either using the 131 sporadic cases alone or in analyses which combined these cases with the 226 unrelated affected AS patients derived from the pedigrees. Analysis of linkage disequilibrium (LD) demonstrated that seven of the eight SNPs studied were in strong LD except for rs626750, which is about 6 kb upstream of the 5' end of the gene. No significant linkage was observed using NPL and LODs in the families. No association was seen of any of the MMP3 SNPs with disease severity (defined by patient functioning), as measured either by the Bath Ankylosing Spondylitis Functional Index or the modified Health Assessment Questionnaire. CONCLUSION: These data suggest that MMP3 genotypes are not involved in AS susceptibility or severity.

Adult↗

Characterization of the protein processing and secretion pathways in a comprehensive set of expressed sequence tags from Trichoderma reesei.

Trichoderma reesei is a filamentous fungus widely used as an efficient protein producer and known to secrete large quantities of biomass degrading enzymes. Much work has been done aimed at improving the secretion efficiency of this fungus. It is generally accepted that the major bottlenecks in secretion are protein folding and ornamentation steps in this pathway. In an attempt to identify genes involved in these steps, the 5' ends of 21888 cDNA clones were sequenced from which a unique set of over 5000 were also 3' sequenced. Using annotation tools Gene Ontology terms were assigned to 2732 of the sequences. Homologs to the majority of Aspergillus niger's Srg genes as well as a number of homologs to genes involved in protein folding and ornamentation pathways were identified.

Computational Biology↗